Distinct changes in the immune systems of patients with ME or chronic fatigue syndrome have been found, say scientists.
Increased levels of immune molecules called cytokines were found in people during the early stages of the disease, a Columbia University study reported.
It said the findings could help improve diagnosis and treatments.
UK experts said further refined research was now needed to confirm the results.
People with ME (myalgic encephalopathy) or CFS (chronic fatigue syndrome) suffer from exhaustion that affects everyday life and does not go away with sleep or rest.
They can also have muscle pain and difficulty concentrating.
ME can also cause long-term illness and disability, although many people improve over time.
It is estimated that around 250,000 people in the UK have the disease.
Disease pattern
The US research team, who published their findings in the journal Science Advances, tested blood samples from nearly 300 ME patients and around 350 healthy people.
They found specific patterns of immune molecules in patients who had the disease for up to three years.
These patients had higher levels of of cytokines, particularly one called interferon gamma, which has been linked to the fatigue that follows many viral infections.
Healthy patients and those who had the disease for longer than three years did not show the same pattern.
Lead author Dr Mady Hornig said this was down to the way viral infections could disrupt the immune system.
"It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop."

By Francis Shen and Dena Gromet
Neuroscience is appearing everywhere. And the legal system is taking notice. The past few years have seen the emergence of “neurolaw.” A spread in the NYT Magazine, a best-selling NYT book, a primetime PBS documentary, the first Law and Neuroscience casebook, and a multimillion-dollar investment from the MacArthur Foundation to fund a Research Network on Law and Neuroscience have all fueled interest in how neuroscience might revolutionize the law.
The potential implications of neurolaw are broad. For example, future developments in brain science might allow: criminal law to better identify recidivists; tort law to better differentiate between those in real pain and those who are faking; insurance law to more accurately and adequately compensate those with mental illness; and end-of-life law to more ethically treat patients who might be able to communicate only through their thoughts. Increasingly courts, including the U.S. Supreme Court, and legislatures are citing brain evidence.
But despite the media coverage, and much enthusiasm from science and legal elites, our new research shows that Americans know very little about neurolaw, and that Republicans and independents may diverge from Democrats in their support for neuroscience based legal reforms.
In our study, we conducted an experiment within a national survey of Americans (more details about the survey are in our article). Everyone in the survey was told that, “Recently developed neuroscientific techniques allow researchers to see inside the human brain as never before.”